Cationic hyperbranched polysaccharide derivative and application of cationic hyperbranched polysaccharide derivative in phototoxicity improvement effect of hematoporphyrin photosensitizers on tumor cells

Abstract

The invention discloses a technique for improving phototoxicity effect of hematoporphyrin photosensitizers on tumor cells by preparing the hematoporphyrin photosensitizer / cationic hyperbranched polysaccharide derivative composite nanoparticles. The composite nanoparticles have the following characteristics and have great application prospect in the field of efficient and safe treatment of tumors through photodynamic: 1) the composite nanoparticles have relatively high tumor cell killing efficiency when the concentration of the hematoporphyrin photosensitizers is relatively low, reduction of the dosage of the hematoporphyrin photosensitizers is facilitated, and the safety of the hematoporphyrin photosensitizers for normal cells and tissue under light irradiation is improved; 2) the composite nanoparticles with the particle size ranging from 200 nm to 250 nm have a passive targeting property for tumor tissue, and the safety of the hematoporphyrin photosensitizers for normal cells and tissue is improved; 3) the composite nanoparticles have the electropositivity, can carry the hematoporphyrin photosensitizers to cross over electronegative cell membranes to enter tumor cells, and accordingly, the endocytosis efficiency of the tumor cells for the hematoporphyrin photosensitizers is improved; 4) the preparation condition is mild, the process is simple, the operation is convenient and the cost is low.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials. More specifically, it relates to a cationic hyperbranched polysaccharide derivative and its application in enhancing the phototoxicity of hematoporphyrin photosensitizers to tumor cells. Background technique [0002] As an emerging tumor tissue localization therapy, photodynamic therapy (Photodynamic Therapy, PDT) has shown certain curative effect in the treatment of skin cancer, gastrointestinal cancer, head and neck tumor, gynecological tumor, etc. (Brown S.B., et al, Lancet Oncol . 2004, 5, 497-508). The principle of treatment is that after intravenous injection of photosensitizer drugs, laser irradiation (wavelength is generally 600-800 nm) is given to the tumor site, and the photosensitizer generates active oxygen (O 2 - and O 2 2- ) or singlet oxygen ( 1 o 2 ) and other phototoxic substances, killing or killing tumor cells, thereby destroying tumor tissue (StojadinovicA....

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Problems solved by technology

[0005] However, due to the following defects of hematoporphyrin photosensitizers, the photodynamic efficacy is affected: (1) The absorption of hematoporphyrin photosensitizers is weak in the red light region. Toxic and side effects on normal tissues are avoided, and a longer photosensitive period is produced on the skin (Yu Kegui et al., Chemical Research and Application, 2007, 19(12), 1298-1303); (2) Hematoporphyrin photosensitizers Lack of tumor tissue targeting, easy to produce toxic side effects on normal tissues (BaeB., et al, Biomaterials, 2010, 31, 6325-6335; Li, S. J., et al, Biomaterials, 2009, 30, 2929–2939); ( 3) Most hematoporphyrin photosensitizers contain -COOH negatively charged groups, which are highly hydrophilic. Because the cell membrane is negatively charged, they are not easy to enter tumor cells (Li Y. et al, Chemistry of Materials 2007, 19, 5557-5562 ; Ding H., et al. Journal of Controlled Release2011, 151, 271–277); (4) hematoporphyrin photosensitizers contain hydrophobic porphin ring and hydrophilic -COOH (that is, they have amphiphilic ), easy to accumulate in the tumor cell membrane, and difficult to enter the tumor cell to exert the effect of photodynamic therapy (Eshghi H., et al, Photodiagnosis and Photodynamic Therapy, 2013, 10, 304-312; Hogset A., et al, Advanced Drug Delivery Reviews, 2004, 56, 95–115)

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